This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Microbes are remarkably resilient. Over time, most microbes can either evolve or acquire mechanisms that allow them to survive in environments that contain high concentrations of toxins. Naturally, the same mechanisms can also lead to microbes becoming highly resistant to antibiotic drugs. As a result, pathogenic microbes are becoming increasingly resistant to once potent pharmaceuticals, with profound consequences for public health. Infections and diseases that were once easily treatable are now difficult, if not impossible, to treat with existing drugs. To address this issues, there is now a pressing need for new pharmaceutical molecules that circumvent antibiotic resistance mechanisms. To meet this need, the Barron group are developing peptidomimentics as a powerful new class of antibiotics. Fully realizing the pharmaceutical potential of peptidomimetics requires an understanding of their mode of action, toxicity and selectivity in bacteria, yeast, and human cells. Soft x-ray tomography, and the other imaging techniques available at the NCXT have been, and will continue to be instrumental in the quest for this knowledge, and in the development of new antimicrobial drugs.